Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 10, Issue -, Pages 4091-4100Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S118457
Keywords
virtual screening; structural optimization; human interlukin-6; small molecular antagonist; XG-7 cells; apoptosis
Categories
Funding
- National Sciences Fund [31070820, 81672368]
- 863 Fund [2012AA02A]
- 973 Fund [2010CB833604]
- China and Beijing Natural Science Fund [5162026]
Ask authors/readers for more resources
According to the three-dimensional (3D) complex structure of (hIL-6.hIL-6R.gp 130)(2) and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD) and MDL Drug Data Report (MDDR), by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available